Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria
Division of Neonatology, Department of Pediatrics and Adolescent Medicine, Pediatric Intensive Care and Neuropediatrics, Medical University of Vienna, Vienna, Austria.
J Leukoc Biol. 2016 Sep;100(3):607-12. doi: 10.1189/jlb.4A0116-001RR. Epub 2016 Mar 10.
Premature infants are highly susceptible to severe bacterial infections. The impaired infection control related to the functional immaturity of the neonatal innate immune system is an important cause of infection. Different monocyte subpopulations have been described and functionally characterized. However, data from preterm infants are scarce. We analyzed constitutive monocyte TLR2, TLR4, CD163, and HLA-DR expression in preterm cord blood. We further investigated activation of the signaling proteins ERK1/2 and NF-κB in monocyte subpopulations after ex vivo stimulation with the bacterial TLR agonists LPS and lipoteichoic acid. The functional outcome of the stimulation was determined by the intracellular production of TNF. Furthermore, the phagocytic activity was measured via flow cytometry. TLR4 and HLA-DR showed a gestational age-dependent increase. However, activation of ERK1/2 and NF-κB was impaired in neonatal monocyte subpopulations after stimulation with TLR agonists. Accordingly, intracellular TNF was diminished in preterm monocytes, especially in nonclassic monocytes. Premature monocytes showed high phagocytic activity, with significantly lower acidification of the phagosome. The reduced functional response of nonclassic monocytes of preterm neonates appears to be part of the diminished early immune response to bacterial cell wall components and is likely to contribute to their susceptibility to bacterial infection.
早产儿极易受到严重细菌感染。由于新生儿先天免疫系统功能不成熟，导致感染控制能力受损，这是感染的一个重要原因。已经描述并功能表征了不同的单核细胞亚群。然而，早产儿的数据很少。我们分析了早产儿脐带血中组成性单核细胞 TLR2、TLR4、CD163 和 HLA-DR 的表达。我们进一步研究了在体外用细菌 TLR 激动剂 LPS 和脂磷壁酸刺激后，单核细胞亚群中 ERK1/2 和 NF-κB 信号蛋白的激活。通过细胞内 TNF 的产生来确定刺激的功能结果。此外，通过流式细胞术测量吞噬活性。TLR4 和 HLA-DR 表现出与胎龄相关的增加。然而，TLR 激动剂刺激后，新生儿单核细胞亚群中 ERK1/2 和 NF-κB 的激活受损。因此，早产儿单核细胞中的细胞内 TNF 减少，尤其是非经典单核细胞。早产儿单核细胞表现出高吞噬活性，吞噬体酸化程度显著降低。早产儿非经典单核细胞功能反应的降低似乎是对细菌细胞壁成分早期免疫反应减弱的一部分，可能导致其易受细菌感染。
